Jeppe Prætorius

Group Leader

Jeppe Prætorius
Professor with special responsibilities in Epithelial Cell Biology
More information 

RESEARCH
The laboratory was started in 2002 and the key interests cover two research areas related to epithelial Na+ transport:
A. (i) to determine the physiological and pathophysiological roles of Na+ dependent HCO3- transporters in various epithelial tissues, and (ii) to define molecular targets for future individualized treatment of human diseases directly or indirectly involving these transporters.
B. (i) To determine the importance of the renal connecting tubule relatively to collecting ducts for the fine-regulation of Na+ reabsorption, and (ii) to uncover fine details in the assembly, subunit composition, maturation, and plasma membrane appearance of the epithelial Na+ channel, ENaC.

The studies involve mapping the specific transmembrane ion transport proteins to specific tissues and subcellular compartments, defining their modes of transport and control of membrane targeting, discovering molecular structure-function relationships, developing tissue-specific gene deletion models for animal experimenting, and determining the therapeutic potential of existing and novel inhibitors of the transporters. The group participates in the training of medical research, bachelor, masters and PhD students.

RESEARCH INTERESTS
Cerebrospinal fluid production and pH regulation: Analyse the relative importance of Ncbe and NBCe2 in cerebrospinal fluid production and pH regulation by the choroid plexus. Determine the possible implications for controlling intracranial pressure, neuronal excitability and respiratory rate in patients with various CNS diseases.

Hypertension: Determine the pathophysiological mechanism behind hypertension caused by NBCe2 mutations or gene deletion. Define molecular targets for controlling transporter expression, trafficking and activity to potentially manipulate systemic blood pressure.

Renal Na+ transport: Describing the phenotypical appearance of mice with tubule-specific gene deletion of ?ENaC. Determine the subunit composition of ENaC complexes, the subcellular site for assembly, the mechanism of RER retention, and the glycosylation and ubiquitination states in vivo after induction by aldosterone.

METHODOLOGIES
Live cell microscopy: dynamic H+, Na+, Cl-, Ca2+ imaging in cells or tissues under physiological conditions. Protein tracking, FRET and BRET protein proximity assays.

Laser scanning confocal microscopy: cellular and subcellular protein localization and co-localization, semi-quantitation of protein abundance and trafficking.

Electron Microscopy: immuno-gold localization of protein(s) in cells or tissues at the nanometer scale.

Eukaryotic expression systems: stable transfection of cell lines with inducible ion transporter genes.

Transgenic mice: global, tissue specific, and inducible transporter gene knockout models or selective GFP expression patterns.

Disease models: animal models for acid/base disturbances and renal Na+ handling.

Protein analysis: immunoblotting, immunohistochemistry, immunocytochemistry.

RNA analysis: RNA purification, RT-PCR, qPCR analysis, promoter studies.

DNA: cloning, genotyping, site-directed mutagenesis.

COLLABORATORS & Centers

  • Helle H Damkier, Robert A Fenton, Birgitte M Christensen, Sebastian Frische, Ole Fejerskov, Christian Aalkjær, Ebbe Bødtkjer Briggs, Department of Biomedicine, Health, AU
  • Ernst-Martin Füchtbauer, Lene Nieman Nejsum, Department of Molecular Biology, Science and Technology, AU
  • Tobias Wang, Department of Biological Sciences, Science and Technology, AU
  • Stine Falsig Petersen, University of Copenhagen, DK
  • Marianne Juhler, Copenhagen University Hospital, Copenhagen, DK
  • J. Preben Morth, University of Oslo, NO
  • Björn Olde, LM Frederik Leeb-Lundberg, Lund University, Lund, SE
  • Ursula Seidler, Hannover Medical School, Hannover, DE
  • Christian A. Hübner, University of Jena, DE
  • Peter D. Brown, University of Manchester, UK
  • Stephen B. Hladky, Margery Berrand, University of Cambridge, UK
  • Edith Hummler, Bernard Rossier, Laurent Schild, Olivier Staub, University of Lausanne, SCH
  • Johannes Loffing, University of Zürich, SCH
  • Joost Hoenderop, Rene Bindels, University of Nijmegen, NL
  • Mark A Knepper, Trairak Pisitkun, Jason Hoffert, National Institutes of Health, Bethesda, MD, USA
  • Dennis Brown, Harvard Medical School, Boston, MA, USA
  • Walter F. Boron, Mark Parker, Case Western School of Medicine, OH, USA
  • Live cell microscopy interest group, Biomedicine, AU
  • Electron microscopy interest group, Biomedicine, AU
  • Danish Center for Transgenic Mice
  • AU-Ideas Pilot Centre InterPrET (Head: R Fenton, AU)       

RESEARCH GROUP MEMBERS
Helle H Damkier, associate professor;  M. Umar Cheema, PhD student; Janne Lebeck, PhD student; Helle Høyer, technician; Christian V. Westberg, technician; Tina Dreyer, technician; Else-Merete Løcke, technician; Bodil Kruse, technician; 2 masters students, 2 research year students, exchange students.

 

Henvendelse om denne sides indhold: 
Revideret 03.08.2016